S1763 Real-World Comparison of Every 6-Week and Every 4-Week Ustekinumab Dose Escalation in Patients With Inflammatory Bowel Disease

Introduction: Several studies have suggested that dose escalation of ustekinumab (UST) from 90 mg subcutaneous every 8 weeks (q8) to every 4 weeks (q4) or 6 weeks (q6) is effective for patients with inflammatory bowel disease (IBD) who do not obtain clinical or biochemical remission, but the decision to escalate to q6 or to q4 week dosing is non-standardized. We aimed to evaluate outcomes in patients with IBD with UST escalation to q6 and q4. Methods: This is a retrospective analysis of patients who underwent UST escalation at our tertiary center between 8/15/2019-4/15/2024. We collected demographics, treatment exposures, steroid use, clinical activity scores, endoscopy findings, biomarkers, and duration of therapy. Treatment success was defined using clinical and objective measures. Statistical comparisons between q6 and q4 week dosing outcomes were performed using Fisher’s Exact Test, Welch’s t-test, and Wilcoxon rank-sum test. Results: 102 patients (71 CD, 29 UC) underwent UST weight based IV loading and maintenance dosing of 90 mg SC q8, but subsequently escalated to q6 (57, 55.9%) or q4 (45, 44.1%). In the q6 group, 52.6% (30/57) remained on therapy for ≥12 months compared to 75.6% (34/45) in the q4 group (P = 0.02). In the q6 group, 17.5% (10/57) transitioned to alternative therapy within 4 months compared to 11.1% (5/45) in the q4 group (P = 0.41). Mean duration of therapy for q6 was significantly shorter than q4 (13.2 vs 20.6 months (P-value = 0.003)). In the q6 group, 49.1% (28/57) achieved steroid free clinical remission (HBI ≤4, SCCAI ≤2, or provider assessment if not documented), vs 71.1% (32/45) in the q4 group (P = 0.03). In the q6 group, 66.7% (12/18) of patients and 76% (19/25) in the q4 group demonstrated mild or no inflammation on post-escalation endoscopic evaluation (P = 0.51). Of patients with elevated CRP pre-escalation, the q6 group had 4/16 patients achieve CRP normalization post-escalation compared to 5/13 patients in the q4 group (P = 0.69). Conclusion: In this real-world cohort of patients with IBD undergoing UST dose interval reduction, escalation to q4 was associated with significantly longer therapy duration and higher rates of steroid-free clinical remission compared to q6. These findings support considering q4 escalation as a preferred strategy for patients requiring UST optimization prior to switching to alternative therapies.